Endothelial and Leukocyte-Derived Microvesicles and Cardiovascular Risk After Stroke: PROSCIS-B.

OBJECTIVE: To determine the role of circulating microvesicles (MV) on long-term cardiovascular outcomes after stroke, we measured them in patients with first-ever stroke with a 3-year follow-up. METHODS: In the Prospective Cohort With Incident Stroke Berlin (PROSCIS-B), patients with first-ever ischemic stroke were followed up for 3 years. The primary combined endpoint consisted of recurrent stroke, myocardial infarction, and all-cause mortality. Citrate-blood levels of endothelial MV (EMV), leukocyte-derived MV (LMV), monocytic MV (MMV), and platelet-derived MV (PMV) were measured with flow cytometry. Kaplan-Meier curves and adjusted Cox proportional hazards models were used to estimate the effect of MV levels on the combined endpoint. RESULTS: Five hundred seventy-one patients were recruited (median age 69 years, 39% female, median NIH Stroke Scale score 2, interquartile range 1-4), and 95 endpoints occurred. Patients with levels of EMV (adjusted hazard ratio [HR] 2.5, 95% confidence interval [CI] 1.2-4.9) or LMV (HR 3.1, 95% CI 1.4-6.8) in the highest quartile were more likely to experience an event than participants with lower levels with the lowest quartile used as the reference category. The association was less pronounced for PMV (HR 1.7, 95% CI 0.9-3.2) and absent for MMV (HR 1.1, 95% CI 0.6-1.8). CONCLUSION: High levels of EMV and LMV after stroke were associated with worse cardiovascular outcome within 3 years. These results reinforce that endothelial dysfunction and vascular inflammation affect the long-term prognosis after stroke. EMV and LMV might play a role in risk prediction for stroke patients. CLINICALTRIALSGOV IDENTIFIER: NCT01363856. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence of the effect of MV levels on subsequent stroke, myocardial infarction, or all-cause mortality in survivors of mild stroke.

Stereoscopic Versus Monoscopic Viewing of Aneurysms: Experience of a Single Institution with a Novel Stereoscopic Viewing System.

OBJECTIVE: Stereoscopic viewing of computed tomographic angiography (CT-A) or magnetic resonance angiograms might increase the diagnostic potential of these imaging techniques. Our aim was to evaluate the benefits of a novel stereoscopic viewing system for aneurysm detection compared with standard monoscopic viewing. METHODS: Retrospective patient data were used for 2 different evaluations. First, monoscopic and stereoscopic CT-A viewing was compared by 14 clinicians in 10 patients with challenging (i.e., small and initially CT-A negative) aneurysms. Second, stereoscopic CT-As and the reference standard, digital subtraction angiography (DSA), were compared in 15 patients with randomly selected aneurysms by 12 clinicians. The study participants rated the presence and location of any aneurysm and its morphological characteristics. The detection rates and interrater reliability were calculated. RESULTS: The first evaluation showed superior aneurysm detection in challenging cases using stereoscopic versus monoscopic CT-A viewing (median: monoscopic, 20%; interquartile range [IQR], 10%-32.5%; stereoscopic, 40%; IQR, 27.5%-42.5%). The interrater reliability analysis revealed good to excellent agreement among raters for aneurysm detection in both viewing modalities (monoscopic, intraclass correlation coefficient [ICC(2,1)], 0.798; 95% confidence interval [CI], 0.549-0.941; stereoscopic viewing, ICC(2,1), 0.895; 95% CI, 0.770-0.968). The second part demonstrated that stereoscopic CT-A viewing is comparable to DSA viewing for aneurysm detection (median: DSA, 80%; IQR, 73%-100%; stereoscopic CT-A, 87%; IQR, 87%-93%). The interrater reliability analysis revealed excellent absolute agreement in aneurysm detection between DSA and stereoscopic CT-A viewing (DSA: ICC(2,1), 0.971; 95% CI, 0.944-0.989; stereoscopic CT-A: ICC(2,1), 0.972; 95% CI, 0.945-0.989). The aneurysm detection rates correlated significantly with the participants' years of experience. CONCLUSIONS: Stereoscopic viewing of CT-As increases the diagnostic accuracy and represents a promising technique to reduce the need for invasive DSA.

Targeting the extradomain A of fibronectin allows identification of vascular resistance to antiangiogenic therapy in experimental glioma.

INTRODUCTION: Clinical application of antiangiogenic therapy lacks direct visualization of therapy efficacy and vascular resistance. We aimed to establish molecular imaging during treatment with sunitinib using the fibronectin extradomain A specific small immunoprotein(SIP)-F8 in glioma. METHODS: Biodistribution analysis of F8-SIP-Alexa-555 was performed in SF126-glioma bearing or control mice (n = 23 and 7, respectively). Intravital microscopy(IVM) was performed on a microvascular level after 7 days (n = 5 per group) and subsequently after 6 days of sunitinib treatment (n = 4) or without (n = 2).Additionally, near infrared fluorescence(NIRF) imaging was established with F8-SIP-Alexa-750 allowing non-invasive imaging with and without antiangiogenic treatment in orthotopic tumors (n = 38 divided in 4 groups). MRI was used to determine tumor size and served as a reference for NIRF imaging. RESULTS: F8-SIP demonstrated a time and hemodynamic dependent tumor specific accumulation. A significantly higher vascular accumulation occurred with antiangiogenic treatment compared to untreated tumors enabling visualization of resistant tumor vessels by F8-SIP-mediated NIRF imaging. In orthotopic tumors, sunitinib reduced F8-SIP-Alexa-750 enrichment volume but not fluorescence intensity indicative of F8-SIP accumulation in fewer vessels. CONCLUSION: F8-SIP is highly tumor specific with time and hemodynamic dependent biodistribution. The higher vascular accumulation to remaining vessels enables molecular imaging and targeting of therapy resistant tumor vessels.